3-d tractography fus ablation for essential tremor

Conditions: Essential Tremor

Summary: the investigators propose to advance vim-fusa (ventral intermediate nucleus - focused ultrasound ablation) with the support of 3-d tractography, a neuroimaging technique to visually represent nerve tracts within the brain. the investigators hypothesize that 3-d tractography vim-fusa will improve the vim ablation compared to standard vim-fusa and prove safe and feasible in the clinical setting. the investigators also hypothesize that intraoperative magnetic resonance (i-mr) monitoring will differentiate ablated tissue from immediate perilesional edema and accurately predict the vim-fusa clinical outcomes.

essential tremor (et) is a common neurological disorder and a leading cause of functional and psychological disabilities that can be difficult to suppress with oral medications, many of which have considerable side effects limiting adequate dosing. as a result, up to 20% of et patients cannot achieve satisfactory control of their symptoms and must consider interventional options. focused ultrasound ablation (fusa) of the ventral intermediate nucleus (vim) is an fda-approved and medicare-reimbursed procedure for et resistant to medications that can selectively ablate the brain area associated with tremor without the need for surgical incisions or anesthesia. the success of vim-fusa depends on the ability to accurately ablate 70% of the vim volume without lesioning neighboring structures, a goal that is complicated by technical challenges in three critical phases of the procedure: planning (identifying the vim location and extension); delivery (ablating the vim volume with adequate accuracy); and monitoring (confirming vim ablation with reliable intraoperative imaging). the investigators propose to advance vim-fusa with the support of 3-d tractography, a neuroimaging technique to visually represent nerve tracts within the brain. the investigators hypothesize that 3-d tractography vim-fusa will improve the vim ablation compared to standard vim-fusa and prove safe and feasible in the clinical setting. the investigators also hypothesize that intraoperative magnetic resonance (i-mr) monitoring will differentiate ablated tissue from immediate perilesional edema and accurately predict the vim-fusa clinical outcomes. aim 1. estimate and characterize the improvement in vim ablation achieved with 3-d tractography vim-fusa vs. standard vim-fusa in an experimental controlled animal study. through an experimental animal study, the investigators will characterize the vim ablation delivered with 3-d tractography vim-fusa in one hemisphere (experimental group) vs. standard vim-fusa in the opposite hemisphere (control group). aim 2. test safety, feasibility, and preliminary efficacy, and estimate effect size of 3-d tractography vim-fusa in a phase-ii, two-groups, pre-post interventional human study. in a human study, the investigators will test the safety and feasibility of ablating 70% of the vim volume while checking for side effects with intraoperative clinical testing. tremor assessments will be videotaped at baseline and 12 weeks and compared, in a blinded fashion, with age-sex matched controls randomly selected from the video repository of the two fda-regulated studies of standard vim-fusa at baseline and 12 weeks. aim 3 (exploratory). assess the accuracy of i-mr in differentiating tissue ablation from immediate perilesional edema and its utility in predicting vim-fusa clinical outcomes. in the experimental animal study, the investigators will estimate and compare the accuracy of conventional and non-conventional i-mr in differentiating tissue necrosis from perilesional edema. in the interventional human study, the investigators will evaluate the utility of i-mr in predicting vim-fusa clinical outcomes

Eligibility criteria:
inclusion criteria: * diagnosis of moderate to severe et agreed upon by at least two movement disorder trained physicians * symptoms refractory to at least two medications * stable medication regimen for at least 4 weeks prior to screening * willing and able to participate in all follow-up visits * willing and able to undergo mr imaging. exclusion criteria: * uncontrolled hypertension * medically unstable coronary artery disease * coagulopathy, anticoagulant therapy, or inability to temporarily stop any antithrombotic medication * tremor disorders other than et * unwilling or unable to undergo tremor surgery while awake * significant and non-correctible motion artifact in imaging * pregnant at the time of enrollment or preoperative evaluation * dementia * history of psychosis * history of drug or alcohol abuse * prior brain surgery such as vim-fusa, deep brain stimulation, and gamma knife thalamotomy * botulinum toxin injection in the tremor-impacted areas three months prior to the baseline assessment and until 3-months after vim-fusa * skull density ratio lower than 0.4 * does not qualify for fda-approved clinical use based on current fda labeling * any significant issue raised by the neurologist or neurosurgeon that may compromise participant safety or potentially interfere with study interpretation.